Lead toxicity: Difference between revisions

(Text replacement - "Pt " to "Patient ")
(Add MedicationDose entries for succimer, dimercaprol, EDTA, penicillamine)
 
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*After weeks mostly in the bones and teeth  
*After weeks mostly in the bones and teeth  
**In adults 94% of total body lead is in the bones and teeth
**In adults 94% of total body lead is in the bones and teeth
*some lead can leave the bones and re-enter blood under certain circumstances
*Some lead can leave the bones and re-enter blood under certain circumstances
**pregnancy, periods of breast feeding, fractures, advanced age
**[[Pregnancy]], periods of breast feeding, fractures, advanced age


=====Metabolism=====
=====Metabolism=====
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**Children retain about 70% while adults only retain about 1%
**Children retain about 70% while adults only retain about 1%


===References===
===Sources===
*Lead paint
*Lead paint
*Occupational  
*Occupational  
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**Eg. Toys imported from China which were coated in lead paints
**Eg. Toys imported from China which were coated in lead paints
**Eg. plates brought by immigrants from Mexico/South America
**Eg. plates brought by immigrants from Mexico/South America
 
*Old gasoline (phased out of gasoline in the 1980s and banned in 1996)
*Phased out of gasoline in the 1980s and banned in 1996


==Clinical Features==
==Clinical Features==
*Vastly different presentations between children and adults
''Vastly different presentations between children and adults''
===Adults===
===Adults===
=====Nervous system=====
=====Nervous system=====
*CNS symptoms predominate
*CNS symptoms predominate
*Lethargy, fatigue, [[headache]], irritability, memory loss, tremor
*[[Lethargy]], fatigue, [[headache]], irritability, memory loss, [[tremor]]
*Severe symptoms: [[AMS]], coma, [[seizures]], cerebral edema
*Severe symptoms: [[altered mental status]], [[coma]], [[seizures]], cerebral edema
*PNS toxicity
*PNS toxicity
**Causes segmental demyelination
**Causes segmental demyelination
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=====Nephro=====
=====Nephro=====
*Highest body levels found in proximal tubules after acute exposure
*Highest body levels found in proximal tubules after acute exposure
**Results in proteinuria, particularly β 2-microglobulin and N-acetylglucosidase.
**Results in [[proteinuria]], particularly β 2-microglobulin and N-acetylglucosidase.
*associated with slightly decreased GFRs
*associated with slightly decreased GFRs


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=====Other=====
=====Other=====
*May also have GI upset, vomiting, constiptation, elevated LFTs
*May also have GI upset, [[vomiting]], [[constipation]], elevated [[LFTs]]
*Myalgias
*[[Myalgia]]s
*associated with increased mortality due to cardiovascular disease
*associated with increased mortality due to cardiovascular disease
*associated with increased blood pressure
*associated with increased blood pressure
*May see thin, blue/black line along gingiva, known as Burton's line (more common in chronic poisoning)


===Children===
===Children===
=====Nervous system=====
=====Nervous system=====
*'''Encephalopathy''' appears at lower levels
*'''[[Encephalopathy]]''' appears at lower levels
*Symptoms: Irritability, apathy, fatigue, obtundation
*Symptoms: Irritability, apathy, fatigue, [[altered mental status (peds)|obtundation]]
*Severe symptoms: Cerebral edema, [[Seizures]]
*Severe symptoms: Cerebral edema, [[Seizures]]
*Can lead to permanent changes in brain architecture
*Can lead to permanent changes in brain architecture
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*Disturbs blood brain barrier permeability which can be chronic
*Disturbs blood brain barrier permeability which can be chronic
*'''Long term sequelae'''
*'''Long term sequelae'''
**Cognitive disturbances (from slight learning disability to profound mental retardation)
**Cognitive disturbances (from slight learning disability to profound intellectual disability)
**Loss of 5 IQ points per 10μg/dL elevation  
**Loss of 5 IQ points per 10μg/dL elevation  
**Hyperactivity, aggression and antisocial behaviors
**Hyperactivity, aggression and antisocial behaviors
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=====Nephro=====
=====Nephro=====
*Impaired [[Vitamin D]] activation
*Impaired [[Vitamin D deficiency|vitamin D]] activation
 
=====Heme=====
=====Heme=====
*Similar to adults
*Similar to adults
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*Lead lines on radiographs
*Lead lines on radiographs
**Generally correlate with levels above 50μg/dL
**Generally correlate with levels above 50μg/dL
*Associated with development of dental carries and periodontal bone loss
*Associated with development of [[dental caries]] and periodontal bone loss
 
==Differential Diagnosis==
{{Heavy metals list}}


==Work-Up==
==Evaluation==
[[File:Lead PoisoningRadio.jpg|thumb|X-ray demonstrating the characteristic finding of dense metaphyseal lines in lead poisoning.]]
[[File:PMC3369416 crg-0006-0243-g03.png|thumb|Lead toxicity resulting from an intra-articular retained [[bullet]].]]
===Work-Up===
*Lead level
*Lead level
*U/A
*[[UA]]
*CBC with smear
*CBC with smear
*Chem 7 and divalents
*Chem 7 and divalents
*LFTs
*[[LFTs]]
*'''''DO NOT LP'''''
*'''''DO NOT [[LP]]'''''
**Cerebral edema may lead to herniation
**Cerebral edema may lead to herniation


*CDC Recommendations for Lead Testing
====CDC Recommendations for Lead Testing====
**at age 1 and 2 years
*at age 1 and 2 years
**at ages 3-6 if never tested for lead
*at ages 3-6 if never tested for lead
**if they received services from public assistance programs for the poor such as Medicaid or WIC
*if they received services from public assistance programs for the poor such as Medicaid or WIC
**if they live in a building or frequently visit a house built before 1978 that has recently been remodeled
*if they live in a building or frequently visit a house built before 1978 that has recently been remodeled
**if they have a brother/sister or playmate who has had lead poisoning
*if they have a brother/sister or playmate who has had lead poisoning


==Diagnosis==
===Diagnosis===
*Lead levels
*Based on lead level


==Treatment==
==Management==
*Environmental Investigations
*Environmental Investigations
**government programs provide intervention for lead levels > 10ug/dl
**government programs provide intervention for lead levels > 10ug/dl
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**Treat children with acute blood Lead levels >45ug/dL or chronic >70ug/dL<ref>Murata K, Iwata T, Dakeishi M, Karita K. Lead toxicity: does the critical level of lead resulting in adverse effects differ between adults and children?. J Occup Health. 2009;51(1):1-12.</ref>
**Treat children with acute blood Lead levels >45ug/dL or chronic >70ug/dL<ref>Murata K, Iwata T, Dakeishi M, Karita K. Lead toxicity: does the critical level of lead resulting in adverse effects differ between adults and children?. J Occup Health. 2009;51(1):1-12.</ref>
**Consider treating symptomatic adults with Lead >50ug/dL or asymptomatic >70ug/dL
**Consider treating symptomatic adults with Lead >50ug/dL or asymptomatic >70ug/dL
*Penicillamine and Succimer
*[[Penicillamine]] and [[Succimer]]
**Oral medications
**Oral medications
**Only used in children <ref>Treatment guidelines for lead exposure in children. American Academy of Pediatrics Committee on Drugs. Pediatrics. Jul 1995;96(1 Patient 1):155-60.</ref>
**Only used in children <ref>Treatment guidelines for lead exposure in children. American Academy of Pediatrics Committee on Drugs. Pediatrics. Jul 1995;96(1 Patient 1):155-60.</ref>
**Succimer has not been studied for Lead levels >60ug/dL
**Succimer has not been studied for Lead levels >60ug/dL
**Succimer 10mg/kg TID x 5d THEN 10mg/kg BID x 14d
**Succimer 10mg/kg TID x 5d THEN 10mg/kg BID x 14d
**Penicillamine: second-line agent, requires B6 supplementation, contraindicated in patients allergic to penicillin, not approved during pregnancy, more toxic than Succimer
**Penicillamine: second or third-line agent, requires B6 supplementation, contraindicated in patients allergic to penicillin, not approved during pregnancy, more toxic than Succimer
**Penicillamine dose: 20-40 mg/kg/day PO divided q8hr
**Penicillamine reported adverse effects include: rash, fever, anorexia, leukopenia, thrombocytopenia, hemolytic anemia, SJS, nephrotoxicity, proteinuria
**Penicillamine reported adverse effects include: rash, fever, anorexia, leukopenia, thrombocytopenia, hemolytic anemia, SJS, nephrotoxicity, proteinuria
*IV/IM EDTA (edetate calcium disodium)
*IM BAL ([[dimercapro]]l)
**do not use as sole agent if encephalopathy present (does not cross blood-brain barrier)
**First line agent if encephalopathy present
***Consider giving first before EDTA, regardless of encephalopathy
***As EDTA, if given first, may chelate lead and cross blood brain barrier
**Onet of action 30 minutes
**Increases fetal excretion of lead as chelated lead is excreted primarily in bile after 4-6 hours
**Also increases urinary excretion of chelated lead
**Agent of choice in renal failure
**Dosage of 50-75mg/m^2 every 4 hours, full course is 3-5 days
**Contraindications: liver failure, G6PD (develop hemolysis), peanut oil allergy, pregnancy
*IV/IM [[EDTA]] (edetate calcium disodium)
**Do not use as sole agent if encephalopathy present (does not cross blood-brain barrier)
**Must have given BAL for at least 4h if Lead >100ug/dL or encephalopathy present
**Must have given BAL for at least 4h if Lead >100ug/dL or encephalopathy present
**increases renal excretion of lead 20-50 times
**Increases renal excretion of lead 20-50 times
**children: 1-1.5gm/m^2/24hrs given in up to 6 divided daily doses
**Children: 1-1.5gm/m^2/24hrs given in up to 6 divided daily doses
**adults: 1.5gm/24hrs in 2 divided doses
**Adults: 1.5gm/24hrs in 2 divided doses
**full course of treatment is 5 days, may be repeated if patient still symptomatic or PbB > 50ug/dl
**Full course of treatment is 5 days, may be repeated if patient still symptomatic or PbB > 50ug/dl
*IM BAL (dimercaprol)
 
**First line agent if encephalopathy present
==Medication Dosing==
**onet of action 30 minutes
{{MedicationDose
**increases fetal excretion of lead as chelated lead is excreted primarily in bile after 4-6 hours
| drug = Succimer
**also increases urinary excretion of chelated lead
| dose = 10mg/kg PO TID x 5 days, then 10mg/kg PO BID x 14 days
**agent of choice in renal failure
| route = PO
**dosage of 50-75mg/m^2 every 4 hours, full course is 3-5 days
| context = Oral chelation, pediatric first-line
**contraindications: liver failure, G6PD (develop hemolysis), peanut oil allergy, pregnancy
| indication = Lead toxicity
| population = Pediatric
}}
{{MedicationDose
| drug = Dimercaprol
| dose = 50-75mg/m2 IM q4hr x 3-5 days
| route = IM
| context = First-line if encephalopathy present
| indication = Lead toxicity
| population = Adult
}}
{{MedicationDose
| drug = EDTA
| dose = 1000-1500mg/m2/day IV continuous infusion x 5 days
| route = IV
| context = Chelation, do not use as sole agent if encephalopathy
| indication = Lead toxicity
| population = Adult
}}
{{MedicationDose
| drug = Penicillamine
| dose = 20-40mg/kg/day PO divided q8hr
| route = PO
| context = Second or third-line oral chelation
| indication = Lead toxicity
| population = Adult
| notes = Contraindicated in penicillin allergy; requires B6 supplementation
}}
 
==Disposition==


==See Also==
==See Also==
*[[Toxicology (main)]]
*[[Heavy Metals]]
*[[Heavy Metals]]


Latest revision as of 21:03, 20 March 2026

Background

  • Stable metallic element (no. 82)
  • Incredible environmental burden secondary to inclusion in paints, fuels, and industrial uses
  • Average blood levels in US have fallen from 12.8 mcg/dL in the late 1970's to 2mcg/dL mostly due to banning lead in gasoline

MOA

  • Interferes with the action of divalent cations and sulfhydryl groups
    • Particularly toxic to Zinc containing enzymes
    • Binds to calcium activated enzymes with 10,000x great affinity that calcium
  • Directly toxic to renal tubules

Toxicokinetics

Absorption
  • Rapidly and completely absorbed from lungs
  • Minimal absorption through intact skin
  • Variable GI absorption
    • Children absorb more than adults (70% vs. 20%)
    • Affected by nutritional status, calcium stores and iron stores
Distribution
  • Large Vd
  • Distributes to bone, muscles, brain, and blood
  • After weeks mostly in the bones and teeth
    • In adults 94% of total body lead is in the bones and teeth
  • Some lead can leave the bones and re-enter blood under certain circumstances
    • Pregnancy, periods of breast feeding, fractures, advanced age
Metabolism
  • No metabolism as toxin is elemental
Excretion
  • Excreted in urine and stool
  • Amount excreted varies with age
    • Children retain about 70% while adults only retain about 1%

Sources

  • Lead paint
  • Occupational
  • Soil contamination
  • Lead dust
  • Water (old pipes, especially when the water is "soft" or acidic)
  • batteries (especially car), weights, ammunition
  • Food (leafy green vegetables grown in lead-containing soil)
  • Moonshine (made in stills that contain lead-soldered parts)
  • Alternative/herbal medications
  • Poorly monitored imported products
    • Eg. Toys imported from China which were coated in lead paints
    • Eg. plates brought by immigrants from Mexico/South America
  • Old gasoline (phased out of gasoline in the 1980s and banned in 1996)

Clinical Features

Vastly different presentations between children and adults

Adults

Nervous system
Nephro
  • Highest body levels found in proximal tubules after acute exposure
    • Results in proteinuria, particularly β 2-microglobulin and N-acetylglucosidase.
  • associated with slightly decreased GFRs
Heme
  • Basophilic stippling
    • From precipitation of nuclear contents
  • Inhibitor of heme synthesis
    • Can lead to either a normochromic or hypochromic anemia
Reproductive
  • Can cross placenta
    • Because lead is stored in bones and there is higher bone turnover during pregnancy, women with previous lead toxicity can have lead intoxicated children despite mother being asymptomatic.
  • Higher rate of stillbirths and spontaneous abortion
  • May cause preterm labor and low birth weights
  • May slow mental development and cause lower intelligence later in childhood
  • Decreased sperm counts
Endocrine
  • changes in T4 and TSH (generally with PbB > 40-60ug/dl)
  • altered levels of testosterone, leutonizing hormone, FSH at PbB > 30-40ug/dl
Other
  • May also have GI upset, vomiting, constipation, elevated LFTs
  • Myalgias
  • associated with increased mortality due to cardiovascular disease
  • associated with increased blood pressure
  • May see thin, blue/black line along gingiva, known as Burton's line (more common in chronic poisoning)

Children

Nervous system
  • Encephalopathy appears at lower levels
  • Symptoms: Irritability, apathy, fatigue, obtundation
  • Severe symptoms: Cerebral edema, Seizures
  • Can lead to permanent changes in brain architecture
    • Inhibits enzymes that mediate arborization of synapses and neuronal cellular adhesion molecules
    • Hippcampus thought to be primary sight of action secondary to high zinc levels
  • Disturbs blood brain barrier permeability which can be chronic
  • Long term sequelae
    • Cognitive disturbances (from slight learning disability to profound intellectual disability)
    • Loss of 5 IQ points per 10μg/dL elevation
    • Hyperactivity, aggression and antisocial behaviors
  • Peripheral neuropathy similar in adults and children[1]
Nephro
Heme
  • Similar to adults
Ortho
  • Disturbs bone development
    • Accelerates skeletal maturation which may predispose to osteoporosis later
  • Lead lines on radiographs
    • Generally correlate with levels above 50μg/dL
  • Associated with development of dental caries and periodontal bone loss

Differential Diagnosis

Evaluation

X-ray demonstrating the characteristic finding of dense metaphyseal lines in lead poisoning.
Lead toxicity resulting from an intra-articular retained bullet.

Work-Up

  • Lead level
  • UA
  • CBC with smear
  • Chem 7 and divalents
  • LFTs
  • DO NOT LP
    • Cerebral edema may lead to herniation

CDC Recommendations for Lead Testing

  • at age 1 and 2 years
  • at ages 3-6 if never tested for lead
  • if they received services from public assistance programs for the poor such as Medicaid or WIC
  • if they live in a building or frequently visit a house built before 1978 that has recently been remodeled
  • if they have a brother/sister or playmate who has had lead poisoning

Diagnosis

  • Based on lead level

Management

  • Environmental Investigations
    • government programs provide intervention for lead levels > 10ug/dl
  • Chelation:
    • Treat children with acute blood Lead levels >45ug/dL or chronic >70ug/dL[2]
    • Consider treating symptomatic adults with Lead >50ug/dL or asymptomatic >70ug/dL
  • Penicillamine and Succimer
    • Oral medications
    • Only used in children [3]
    • Succimer has not been studied for Lead levels >60ug/dL
    • Succimer 10mg/kg TID x 5d THEN 10mg/kg BID x 14d
    • Penicillamine: second or third-line agent, requires B6 supplementation, contraindicated in patients allergic to penicillin, not approved during pregnancy, more toxic than Succimer
    • Penicillamine dose: 20-40 mg/kg/day PO divided q8hr
    • Penicillamine reported adverse effects include: rash, fever, anorexia, leukopenia, thrombocytopenia, hemolytic anemia, SJS, nephrotoxicity, proteinuria
  • IM BAL (dimercaprol)
    • First line agent if encephalopathy present
      • Consider giving first before EDTA, regardless of encephalopathy
      • As EDTA, if given first, may chelate lead and cross blood brain barrier
    • Onet of action 30 minutes
    • Increases fetal excretion of lead as chelated lead is excreted primarily in bile after 4-6 hours
    • Also increases urinary excretion of chelated lead
    • Agent of choice in renal failure
    • Dosage of 50-75mg/m^2 every 4 hours, full course is 3-5 days
    • Contraindications: liver failure, G6PD (develop hemolysis), peanut oil allergy, pregnancy
  • IV/IM EDTA (edetate calcium disodium)
    • Do not use as sole agent if encephalopathy present (does not cross blood-brain barrier)
    • Must have given BAL for at least 4h if Lead >100ug/dL or encephalopathy present
    • Increases renal excretion of lead 20-50 times
    • Children: 1-1.5gm/m^2/24hrs given in up to 6 divided daily doses
    • Adults: 1.5gm/24hrs in 2 divided doses
    • Full course of treatment is 5 days, may be repeated if patient still symptomatic or PbB > 50ug/dl

Medication Dosing

Succimer 10mg/kg PO TID x 5 days, then 10mg/kg PO BID x 14 days PO Dimercaprol 50-75mg/m2 IM q4hr x 3-5 days IM EDTA 1000-1500mg/m2/day IV continuous infusion x 5 days IV Penicillamine 20-40mg/kg/day PO divided q8hr PO — Contraindicated in penicillin allergy; requires B6 supplementation

Disposition

See Also

References

  1. ↑ Lead exposure in children: prevention, detection, and management. Pediatrics. Oct 2005;116(4):1036-46.
  2. ↑ Murata K, Iwata T, Dakeishi M, Karita K. Lead toxicity: does the critical level of lead resulting in adverse effects differ between adults and children?. J Occup Health. 2009;51(1):1-12.
  3. ↑ Treatment guidelines for lead exposure in children. American Academy of Pediatrics Committee on Drugs. Pediatrics. Jul 1995;96(1 Patient 1):155-60.


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